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2011 Grants

The Role of Mononuclear Phagocytes in Alzheimer's Disease

2011 Multi-Centered Project Grant

The term mononuclear phagocyte (MNP) is used to describe a broad class of cells that have a single central region (nucleus) and that remove debris from tissues (phagocytosis). Cells that perform this function are often considered part of the immune system, even though they can be found in any tissue of the body, including the brain.

The main MNPs in the brain are called microglia. In the brains of persons with Alzheimer's disease, microglia are abnormally active, and there is evidence that they migrate to areas containing amyloid plaques, one of the hallmarks of Alzheimer's pathology. Furthermore, activated microglia secrete hormone-like substances that promote inflammation, another prominent feature of Alzheimer's.

Another group of MNPs are called monocyte-derived macrophages. Monocytes are found throughout the body. Signals that are still not well understood stimulate the entry of monocytes into the brain, where they change into another type of immune-related cell called macrophages. Macrophages serve to engulf and then digest debris that may be found in the brain and they may contribute to the disease process. There is evidence, for example, that monocyte-derived macrophages may contribute to the development of Alzheimer's brain changes in ways distinct from microglia.

Four investigators from the Cleveland Clinic and Case Western Reserve University have proposed a collaborative research project to study the roles of microglia and macrophages in the development of various aspects of Alzheimer's pathology. Details of each investigator's research plan can be found in the descriptions of the component projects by Dr. Bruce T. Lamb, Dr. Sanjay W. Pimplikar, Dr. Richard M. Ransohoff and Dr. Daniel Wesson. Considered together, the results of these studies are expected to yield new insights into the mechanisms by which inflammatory signals and cells of the immune system contribute to the development of Alzheimer's disease.